K. Sueyoshi et al. / Tetrahedron 72 (2016) 5472e5478
5477
30 min, a solution of 7a (4.2 g, 15.4 mmol) in CH2Cl2 (53 mL) was
added dropwise and stirred at ꢀ78 ꢁC for 1.5 h i-Pr2NEt (21.5 mL,
123.2 mmol) was added and the reaction mixture was stirred at
0 ꢁC for 30 min. The mixture was quenched with aqueous saturated
NH4Cl. The whole was extracted with CH2Cl2 and the extract was
washed with brine, dried over MgSO4. The filtrate was concentrated
under reduced pressure to give the corresponding aldehyde, which
was used without further purification. To a stirred solution of the
above aldehyde in CH2Cl2 (118 mL) and Et2O (11.8 mL) under argon
were added diene 8 and BF3$OEt2 (2.9 mL, 23.1 mmol) at ꢀ78 ꢁC.
After stirring for 2 h, a mixture of THF/H2O/1N HCl (5:1:0.4 v/v,
77 mL) was added to the reaction mixture. The mixture was
warmed to room temperature and stirred for 15 min. Then, aqueous
saturated NaHCO3 was added to the mixture at 0 ꢁC. The whole was
extracted with CH2Cl2 and the extract was washed with brine, dried
over MgSO4. The filtrate was concentrated under reduced pressure
and the residue was purified by flash chromatography over silica
over silica gel with hexane-EtOAc (5:1 to 2:1) to give compound 11a
26
(130.6 mg, 81%) as a colorless oil: [
a
]
e6.85 (c 0.95, CHCl3); IR
D
(neat) 3362, 1712 cmꢀ1 1H NMR (500 MHz, CDCl3)
;
d 0.79 (d,
J¼6.9 Hz, 3H), 0.85 (d, J¼6.9 Hz, 3H), 0.91 (t, J¼7.2 Hz, 3H),1.24e1.42
(m, 4H), 1.67e1.75 (m, 2H), 1.87 (s, 3H), 2.35e2.41 (m, 1H),
2.46e2.51 (m, 1H), 2.82 (br s, 1H), 3.54 (dd, J¼9.5, 2.0 Hz, 1H), 3.74
(s, 3H), 3.82 (td, J¼7.7, 3.4 Hz,1H), 4.04 (br s,1H), 6.91e6.95 (m,1H);
13C NMR (125 MHz, CDCl3)
d 11.8, 12.7, 12.9, 14.2, 20.4, 34.2, 34.6,
36.4, 40.7, 51.7, 75.9, 79.6, 129.4, 138.8, 168.5; HRESIMS m/z
[MþNa]þ 295.1870 (calcd for C15H28O4Na, 295.1880).
4.8.6. Methyl
(E)-2-methyl-4-{(4S,5S,6R)-2,2,5-trimethyl-6-[(S)-
pentan-2-yl]-1,3-dioxan-4-yl}but-2-enoate (12a). To a stirred solu-
tion of 11a (100.0 mg, 0.37 mmol) in CH2Cl2 (3.7 mL) under argon
were added 2,2-dimethoxypropane (0.453 mL, 3.7 mmol) and PPTS
(93.0 mg, 0.37 mmol) at room temperature. After stirring for 3 h,
the reaction mixture was quenched with aqueous saturated
NaHCO3. The whole was extracted with CH2Cl2 and the extract was
washed with brine, dried over MgSO4. The filtrate was concentrated
under reduced pressure and the residue was purified by flash
chromatography over silica gel with hexane-EtOAc (15:1) to give
gel with hexane-EtOAc (20:1 to 10:1) to give compound 9a (5.1 g,
26
85%) as a colorless oil: [
a]
e0.35 (c 1.02, CHCl3); IR (neat) 3503,
D
1716 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d 0.10 (s, 3H), 0.12 (s, 3H),
0.88e0.92 (m, 15H), 1.02 (d, J¼7.4 Hz, 3H), 1.04e1.12 (m, 1H),
1.15e1.26 (m, 1H), 1.33e1.41 (m, 1H), 1.42e1.49 (m, 1H), 1.66e1.70
(m, 1H), 1.71e1.77 (m, 1H), 1.87 (s, 3H), 2.20e2.26 (m, 1H),
2.39e2.45 (m, 1H), 3.54e3.57 (m, 2H), 3.73 (s, 3H), 4.21e4.24 (m,
compound 12a (103.6 mg, 90%) as a colorless oil: [
a]
D
26 e2.27 (c 0.78,
CHCl3); IR (neat) 1715 cmꢀ1 1H NMR (500 MHz, CDCl3)
;
d 0.75 (d,
J¼6.3 Hz, 3H), 0.83 (d, J¼6.3 Hz, 3H), 0.88e0.91 (m, 3H), 1.23e1.33
(m, 4H), 1.34 (s, 3H), 1.39 (s, 3H), 1.45e1.52 (m, 1H), 1.64e1.68 (m,
1H), 1.84 (d, J¼1.1 Hz, 3H), 2.26e2.32 (m, 1H), 2.46e2.51 (m, 1H),
3.42 (dd, J¼10.0, 2.0 Hz, 1H), 3.57 (dt, J¼12.8, 4.4 Hz, 1H), 3.74 (s,
1H), 6.78e6.81 (m, 1H); 13C NMR (125 MHz, CDCl3)
12.2, 12.6, 14.3, 16.4, 18.3, 20.7, 26.1 (3C), 34.2, 35.4, 37.6, 37.8, 51.7,
70.4, 83.0, 129.0, 138.8, 168.4; HRESIMS m/z [MþNa]þ 409.2744
(calcd for C21H42O4SiNa, 409.2745).
d
ꢀ3.9, e3.8,
3H), 6.85e6.88 (m, 1H); 13C NMR (125 MHz, CDCl3)
d 11.8, 12.5, 12.6,
14.3, 19.4, 20.4, 30.0, 32.7, 32.9, 35.3, 36.2, 51.7, 74.0, 75.7, 97.8,
4.8.4. Methyl (5S,6S,7R,8S,E)-7-(tert-butyldimethylsilyloxy)-5-
hydroxy-2,6,8-trimethylundec-2-enoate (10a). To a stirred solution
of 9a (10.7 g, 27.8 mmol) in CH2Cl2 (199 mL) under argon was added
DesseMartin periodinane (17.7 g, 41.7 mmol) at room temperature.
After stirring for 1 h, the reaction mixture was quenched with
aqueous saturated NaHCO3 and Na2S2O3. The whole was extracted
with CH2Cl2 and the extract was washed with brine, dried over
MgSO4. The filtrate was concentrated under reduced pressure and
the residue was purified by flash chromatography over silica gel with
hexane-EtOAc (25:1 to 15:1) to give the corresponding ketone,
which was used without further purification. To a stirred solution of
the above ketone in MeOH (263 mL) under argon was added NaBH4
(6.0 g, 157.8 mmol) at ꢀ78 ꢁC. After stirring for 20 h, the reaction
mixture was quenched with aqueous saturated NH4Cl and concen-
trated under reduced pressure. The residue was extracted with
EtOAc and the extract was washed with brine, dried over MgSO4. The
filtrate was concentrated under reduced pressure and the residue
was purified by flash chromatography over silica gel with hexane-
128.5, 139.2, 168.6; HRESIMS m/z [MþNa]þ 335.2186 (calcd for
C18H32O4Na, 335.2193).
4.8.7. (E)-2-Methyl-4-{(4S,5S,6R)-2,2,5-trimethyl-6-[(S)-pentan-2-
yl]-1,3-dioxan-4-yl}but-2-en-1-ol (13a). To a stirred solution of 12a
(87.0 mg, 0.28 mmol) in THF (2.8 mL) under argon was added DIBAL
(1.0 M in toluene; 0.84 mL, 0.84 mmol) at ꢀ78 ꢁC. After stirring for
3 h, a saturated aqueous solution of sodium potassium tartrate was
added to the reaction mixture and the mixture was stirred at room
temperature for 1 h. The whole was extracted with Et2O and the
extract was washed with brine, dried over MgSO4. The filtrate was
concentrated under reduced pressure and the residue was purified
by flash chromatography over silica gel with hexane-EtOAc (7:1 to
27
4:1) to give compound 13a (71.7 mg, 90%) as a colorless oil: [
e1.60 (c 1.03, CHCl3); IR (neat) 3317 cmꢀ1
CDCl3)
a
]
D
;
1H NMR (500 MHz,
d
0.74 (d, J¼6.9 Hz, 3H), 0.82 (d, J¼6.9 Hz, 3H), 0.88e0.90 (m,
3H), 1.18e1.34 (m, 4H), 1.34 (s, 3H), 1.38 (s, 3H), 1.43e1.51 (m, 1H),
1.64e1.67 (m, 5H), 2.12e2.17 (m, 1H), 2.36e2.40 (m, 1H), 3.40 (dd,
J¼10.3, 2.3 Hz, 1H), 3.47e3.52 (m, 1H), 4.01 (s, 2H), 5.52e5.55 (m,
EtOAc (10:1) to give compound 10a (8.9 g, 83%, dr>97:3) as a color-
27
less oil: [
a
]
e9.16 (c 1.18, CHCl3); IR (neat) 3522, 1716 cmꢀ1
;
1H
1H); 13C NMR (125 MHz, CDCl3)
d 11.8, 12.5, 13.9, 14.3, 19.5, 20.4,
D
NMR (500 MHz, CDCl3)
d
0.10 (s, 3H), 0.12 (s, 3H), 0.85 (d, J¼6.9 Hz,
30.0, 31.5, 32.7, 35.1, 36.2, 68.9, 74.6, 75.8, 97.7, 122.5, 135.9; HRE-
3H), 0.88e0.93 (m, 15H), 1.11e1.17 (m, 1H), 1.22e1.29 (m, 1H),
1.33e1.41 (m, 2H), 1.58e1.64 (m, 1H), 1.73e1.77 (m, 1H), 1.86 (s, 3H),
2.26e2.32 (m, 1H), 2.42e2.44 (m, 1H), 3.49 (dd, J¼5.4, 3.7 Hz, 1H),
SIMS m/z [MþNa]þ 307.2247 (calcd for C17H32O3Na, 307.2244).
4.8.8. (5S,6S,7R,8S,E)-2,6,8-Trimethylundec-2-ene-1,5,7-triol
(4a). To a stirred solution of 13a (50.6 mg, 0.18 mmol) in MeOH
(3.2 mL) was added 1N HCl (0.54 mL, 0.54 mmol) at room tem-
perature. After stirring overnight, the reaction mixture was
quenched with aqueous saturated NaHCO3. The whole was
extracted with EtOAc and the extract was washed with brine, dried
over MgSO4. The filtrate was concentrated under reduced pressure
and the residue was purified by flash chromatography over silica
3.52 (s, 1H), 3.68e3.71 (m, 1H), 3.73 (s, 3H), 6.94e6.97 (m, 1H); 13
C
NMR (125 MHz, CDCl3)
d
ꢀ4.2, e3.9, 12.7, 14.3, 14.8, 16.1, 18.2, 20.7,
26.0 (3C), 33.5, 35.5, 38.6, 41.9, 51.6, 73.0, 81.5, 128.7, 139.3, 168.5;
HRESIMS m/z [MþNa]þ 409.2743 (calcd for C21H42O4SiNa, 409.2745).
4.8.5. Methyl (5S,6S,7R,8S,E)-5,7-dihydroxy-2,6,8-trimethylundec-2-
enoate (11a). To a stirred solution of 10a (229.4 mg, 0.59 mmol)
in THF (5.9 mL) under argon was added TBAF (1 M in THF; 1.8 mL,
1.8 mmol) at room temperature. After stirring for 3 h, the reaction
mixture was quenched with aqueous saturated NH4Cl. The whole
was extracted with Et2O and the extract was washed with brine,
dried over MgSO4. The filtrate was concentrated under reduced
pressure and the residue was purified by flash chromatography
gel with hexane-EtOAc (3:1 to 1:2) to give compound 4a (22.5 mg,
29
51%) as a colorless oil: [
a]
e2.82 (c 1.00, CHCl3); IR (neat)
0.80 (d, J¼6.9 Hz, 3H),
D
3348 cmꢀ1
;
1H NMR (500 MHz, CD3OD)
d
0.83 (d, J¼6.9 Hz, 3H), 0.90e0.93 (m, 3H), 1.24e1.29 (m, 1H),
1.32e1.40 (m, 3H), 1.60e1.67 (m, 1H), 1.67 (s, 3H), 1.74e1.82 (m, 1H),
2.12e2.18 (m, 1H), 2.27e2.31 (m, 1H), 3.41 (dd, J¼9.7, 2.3 Hz, 1H),